The overall objective of the proposed study is to determine the control of pancreatic somatostatin secretion and to elucidate secretion modulating influences among endogenous somatostatin, glucagon, and insulin. The initial objective is to study stimuli which regulate pancreatic somatostatin release in an in vivo and an in vitro system. The in vivo model consists of determining the accumulation or depletion rate of pancreatic somatostatin under the influence of various neuropharmacological agents. The in vitro model consists of directly studying the release of somatostatin from isolated islets under the influence of various neuropharmacological agents and other presumed secretogogues. The objective of determining islet paracrine influences will be carried out by studying secretion of insulin, glucagon and somatostatin from isolated islets incubated in the presence of antibodies to one or more of the hormones. The long term objective of this study is to 1) establish those factors which control somatostatin secretion and 2) establish the extent and conditions whereby endogeneous somatostatin modulates insulin and glucagon secretion.